Silica-Induced Lung and Systemic Inflammation Was Prevented by Pretreatment with a Water-Soluble, Organosilane-Based Coating in an Animal Model

Details

• Personal Author:
  Antonini JM ; Arnold E ; Bowers L ; Boyce G ; Kodali V ; Meighan TG ; Roach KA ; Roberts, Jennifer R. ; Shoeb M ; Stefaniak, Aleksandr B.
• Description:
  Background and Purpose: Inhalation exposure of respirable crystalline silica puts thousands of workers from multiple industries at risk for pulmonary disease. Inhalation of silica dust can cause pulmonary fibrosis and inflammation, chronic obstructive lung disease, and lung cancer. One of the primary causes of silica-induced lung disease is the highly reactive surface of fractured silica particles which generates cell-damaging reactive oxygen species. Coating silica particles with specific organosilanes has been shown to reduce silica-induced toxicity in lung macrophages in vitro. The objective of the current study was to use an in vivo model to evaluate acute and sub-chronic toxicity and the resolution kinetics in lungs induced after silica exposure with and without a specific water-soluble, organosilane-based coating (SIVO160). Methods: Male Sprague-Dawley rats were intratracheally instilled with silica (1 mg/rat), silica coated with SIVO160, SIVO160 alone, or saline (vehicle control). At 3, 10, 45, and 90 d after exposure, bronchoalveolar lavage (BAL) was performed to assess lung inflammation and injury. Whole blood was collected at each of the time points post-exposure to evaluate systemic inflammation by differentiating circulating white blood cells. In addition, samples of uncoated and coated silica were analyzed by different methods [(1) RapiFlex MALDI-ToF/ToF mass spectrometry; (2) digestion in phagolysosomal simulant fluid (PSF; pH 4.5; model of lung macrophage phagolysosome) and serum ultrafiltrate (SUF; pH 7.3; model of extracellular lung lining fluid)] to confirm the SIVO160 coating on the surface of the silica particles after an extended incubation period in biological media. Results: At each time point after exposure, silica significantly increased BAL fluid lactate dehydrogenase (lung injury) and the number of recovered lung macrophages and neutrophils (lung inflammation) compared to the saline-treated controls. These silica-induced elevations in lung toxicity were completely blocked at each time point when silica was coated with SIVO160 before exposure. Pulmonary exposure to SIVO160 alone produced no increase in lung injury and inflammation. Changes in peripheral blood phenotypes were not observed until 45 d after silica exposure as total white blood cells, neutrophils, and lymphocytes were significantly elevated in the blood compared to the other groups. Coating the silica with SIVO160 before exposure prevented the observed changes in blood cell profiles. As assessed by mass spectrometry, multiple unique spectral peaks were detected on the surface of the silica+SIVO160 particle samples after an overnight incubation in saline. The peaks were absent in the uncoated silica sample spectra, confirming the coating's presence on the particles. The removal of the SIVO160 coating on the silica had a delay of approximately 3 d after incubation in both PSF and SUF, suggesting some protection could be conveyed to lung cells by the coating during phagocytosis and particle deposition on lung tissue structures. Microscopic evaluation of tissue slices showed that particles were still visible at 90 d within lung cells of the animals treated with uncoated silica but were not present in the lungs of the animals treated with silica coated with SIVO160. This indicated the coated silica was likely not toxic to phagocytes and was cleared from the lungs, whereas the uncoated silica persisted in the lungs throughout the course of the study. Conclusions: SIVO160 coating of highly toxic silica particles: (1) prevented lung and systemic toxicity at both acute and sub-chronic time points after exposure; (2) increased the rate of clearance of the deposited particles compared to uncoated particles from the lungs; and (3) persisted on the surface of the particles in different simulated biological fluids. Organosilane materials may be used as a possible mitigation strategy to potentially protect large numbers of workers exposed to crystalline silica in multiple industries. [Description provided by NIOSH]
• Subjects:
  Immune System Laboratories Lung Occupational Health Respiratory System Safety Silicon Dioxide
• Keywords:
  Coatings Crystalline Silica Immune Reaction Inhalation In Vivo Study Laboratory Animals Pulmonary Effects
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  198
• NIOSHTIC Number:
  nn:20069350
• Citation:
  Toxicologist 2024 Mar; 198(S1):487
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Oil and Gas Extraction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:04f30519d9dcc5c77964c84582d3bd455ab06bb9e3756aad7d5b17a17a0e9bb19752391966bd66864eaa25cef61f70fb689b59a307df51cda73518edff2e7517
• Download URL:
  https://stacks.cdc.gov/view/cdc/207847/cdc_207847_DS1.pdf
• File Type:
  [PDF - 519.91 KB ]